Serum BDNF as an Objective Indicator of Rehabilitation Response in Patients with Subacute Stroke

Background/Objectives: Serum brain-derived neurotrophic factor (BDNF) is linked to post-stroke neuroplasticity, but its temporal dynamics and clinical relevance during early rehabilitation remain unclear. We investigated changes in serum mature BDNF, proBDNF, and matrix metalloproteinase-9 (MMP-9) during the early subacute phase of stroke and their associations with functional improvement under standardized inpatient rehabilitation. Methods: In this prospective observational study at a tertiary inpatient rehabilitation unit, 100 stroke patients were enrolled and 84 were analyzed. Serum biomarkers and clinical assessments—including the National Institutes of Health Stroke Scale (NIHSS), Korean Mini-Mental State Examination, Fugl-Meyer Assessment, and Berg Balance Scale—were obtained at baseline (T0) and after two weeks of rehabilitation (T1). Correlation and multivariable regression analyses examined relationships between biomarker changes and functional outcomes, adjusting for age, sex, time from onset, and BDNF genotype. Results: An increase in serum mature BDNF from T0 to T1 was significantly associated with NIHSS improvement (r = −0.273, p = 0.014), which persisted after multivariable adjustment (β = −0.737, p = 0.009). Changes in proBDNF and MMP-9 showed no significant associations. Conclusions: Greater individual increases in serum mature BDNF during early subacute rehabilitation were independently associated with greater reductions in stroke severity, whereas the group-level mean did not increase over time. Serum mature BDNF may serve as a time-sensitive, objective biomarker of neurobiological recovery, potentially supporting individualized rehabilitation strategies.